Beltz L A, Sztein M B, Kierszenbaum F
Department of Microbiology and Public Health, Michigan State University, East Lansing 48824.
J Immunol. 1988 Jul 1;141(1):289-94.
Co-culture of blood forms of Trypanosoma cruzi, the causative agent of Chagas' disease, with human PBMC impaired the capacity of T lymphocytes to express surface receptors for IL-2. This effect was evidenced by marked reductions in both the proportion of Tac+ cells and the density of Tac Ag on the surface of the positive cells, determined by flow cytometry. The extent of the inhibition increased with parasite concentration. Under optimal or suboptimal conditions of stimulation with either PHA or monoclonal anti-CD3, specific for an epitope of the T3-Ti human T cell Ag receptor complex, the presence of T. cruzi curtailed the capacity of T lymphocytes to proliferate and express Il-2R but did not affect IL-2 production. Furthermore, the addition of exogenous IL-2 did not restore the responsiveness of suppressed human lymphocytes but did when mouse lymphocytes were used instead. Therefore, unlike mouse lymphocytes, human lymphocyte suppression by T. cruzi did not involve deficient IL-2 production and was accompanied by impaired IL-2 utilization. Co-culture of human monocytes/macrophages with suppressive concentrations of T. cruzi increased IL-1 production, and the parasite did not decrease IL-1 secretion stimulated by a bacterial LPS. Therefore, the suppression of IL-2R expression and lymphoproliferation is not likely to have been an indirect consequence of insufficient IL-1 production due to infection of monocytes or macrophages. We have shown that suppression of human lymphocyte proliferation by T. cruzi is not caused by nutrient consumption, absorption of IL-2, lymphocyte killing, or mitogen removal by the parasite. Therefore, these results uncover a novel suppressive mechanism induced by T. cruzi, involving inhibited expression of IL-2R after lymphocyte activation and rendering T cells unable to receive the IL-2 signal required for continuation of their cell cycle and mounting effective immune responses.
恰加斯病的病原体克氏锥虫的血液型与人类外周血单核细胞（PBMC）共培养会损害T淋巴细胞表达白细胞介素-2（IL-2）表面受体的能力。通过流式细胞术测定，Tac⁺细胞比例和阳性细胞表面Tac抗原密度的显著降低证明了这种效应。抑制程度随寄生虫浓度增加而增大。在用对T3-Ti人T细胞抗原受体复合物表位具有特异性的PHA或单克隆抗CD3进行最佳或次最佳刺激条件下，克氏锥虫的存在会抑制T淋巴细胞增殖和表达IL-2受体，但不影响IL-2的产生。此外，添加外源性IL-2不能恢复被抑制的人类淋巴细胞的反应性，但用小鼠淋巴细胞代替时则可以恢复。因此，与小鼠淋巴细胞不同，克氏锥虫对人类淋巴细胞的抑制并不涉及IL-2产生不足，而是伴随着IL-2利用受损。人类单核细胞/巨噬细胞与抑制浓度的克氏锥虫共培养会增加IL-1的产生，并且该寄生虫不会降低细菌脂多糖刺激的IL-1分泌。因此，IL-2受体表达和淋巴细胞增殖的抑制不太可能是由于单核细胞或巨噬细胞感染导致IL-1产生不足的间接后果。我们已经表明，克氏锥虫对人类淋巴细胞增殖的抑制不是由营养消耗、IL-2吸收、淋巴细胞杀伤或寄生虫去除丝裂原引起的。因此，这些结果揭示了克氏锥虫诱导的一种新的抑制机制，涉及淋巴细胞激活后IL-2受体表达受抑制，使T细胞无法接收其细胞周期延续和产生有效免疫反应所需的IL-2信号。
